TY3H_DROME
ID TY3H_DROME Reviewed; 579 AA.
AC P18459; Q24000; Q8SY95;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 28-FEB-2003, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Tyrosine 3-monooxygenase;
DE EC=1.14.16.2;
DE AltName: Full=Protein Pale;
DE AltName: Full=Tyrosine 3-hydroxylase;
DE Short=TH;
GN Name=ple; Synonyms=TH; ORFNames=CG10118;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS NEURONAL AND
RP HYPODERMAL).
RX PubMed=2483109; DOI=10.1016/0896-6273(89)90183-9;
RA Neckameyer W.S., Quinn W.G.;
RT "Isolation and characterization of the gene for Drosophila tyrosine
RT hydroxylase.";
RL Neuron 2:1167-1175(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM NEURONAL).
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
CC -!- FUNCTION: Plays an important role in the physiology of adrenergic
CC neurons.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tyrosine + O2 =
CC (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + L-dopa;
CC Xref=Rhea:RHEA:18201, ChEBI:CHEBI:15379, ChEBI:CHEBI:15642,
CC ChEBI:CHEBI:57504, ChEBI:CHEBI:58315, ChEBI:CHEBI:59560;
CC EC=1.14.16.2;
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC -!- ACTIVITY REGULATION: Phosphorylation leads to an increase in the
CC catalytic activity. {ECO:0000250|UniProtKB:P07101}.
CC -!- PATHWAY: Catecholamine biosynthesis; dopamine biosynthesis; dopamine
CC from L-tyrosine: step 1/2.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P24529}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P24529}. Note=Expressed in dopaminergic axons
CC and axon terminals. {ECO:0000250|UniProtKB:P24529}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Neuronal;
CC IsoId=P18459-1; Sequence=Displayed;
CC Name=Hypodermal;
CC IsoId=P18459-2; Sequence=VSP_000545;
CC -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid
CC hydroxylase family. {ECO:0000305}.
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DR EMBL; U14395; AAA62876.1; -; Genomic_DNA.
DR EMBL; U14395; AAA62877.1; -; Genomic_DNA.
DR EMBL; X76209; CAA53802.1; -; mRNA.
DR EMBL; AE014296; AAN12080.1; -; Genomic_DNA.
DR EMBL; AE014296; AAF50648.1; -; Genomic_DNA.
DR EMBL; AY071698; AAL49320.1; -; mRNA.
DR PIR; A55369; A55369.
DR RefSeq; NP_001286955.1; NM_001300026.1. [P18459-1]
DR RefSeq; NP_476897.1; NM_057549.3. [P18459-2]
DR RefSeq; NP_476898.1; NM_057550.4. [P18459-1]
DR AlphaFoldDB; P18459; -.
DR SMR; P18459; -.
DR BioGRID; 64196; 27.
DR DIP; DIP-17399N; -.
DR IntAct; P18459; 2.
DR STRING; 7227.FBpp0076666; -.
DR iPTMnet; P18459; -.
DR PaxDb; P18459; -.
DR PRIDE; P18459; -.
DR EnsemblMetazoa; FBtr0076956; FBpp0076665; FBgn0005626. [P18459-2]
DR EnsemblMetazoa; FBtr0076957; FBpp0076666; FBgn0005626. [P18459-1]
DR EnsemblMetazoa; FBtr0345585; FBpp0311654; FBgn0005626. [P18459-1]
DR GeneID; 38746; -.
DR KEGG; dme:Dmel_CG10118; -.
DR CTD; 18809; -.
DR FlyBase; FBgn0005626; ple.
DR VEuPathDB; VectorBase:FBgn0005626; -.
DR eggNOG; KOG3820; Eukaryota.
DR GeneTree; ENSGT00950000182885; -.
DR InParanoid; P18459; -.
DR OMA; PELDMNH; -.
DR PhylomeDB; P18459; -.
DR Reactome; R-DME-209905; Catecholamine biosynthesis.
DR SignaLink; P18459; -.
DR UniPathway; UPA00747; UER00733.
DR BioGRID-ORCS; 38746; 0 hits in 3 CRISPR screens.
DR ChiTaRS; ple; fly.
DR GenomeRNAi; 38746; -.
DR PRO; PR:P18459; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0005626; Expressed in saliva-secreting gland and 28 other tissues.
DR ExpressionAtlas; P18459; baseline and differential.
DR Genevisible; P18459; DM.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004511; F:tyrosine 3-monooxygenase activity; IBA:GO_Central.
DR GO; GO:0048085; P:adult chitin-containing cuticle pigmentation; IMP:FlyBase.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:FlyBase.
DR GO; GO:0006584; P:catecholamine metabolic process; NAS:UniProtKB.
DR GO; GO:0007619; P:courtship behavior; NAS:FlyBase.
DR GO; GO:0048067; P:cuticle pigmentation; IMP:FlyBase.
DR GO; GO:0048066; P:developmental pigmentation; TAS:FlyBase.
DR GO; GO:0042416; P:dopamine biosynthetic process; IMP:FlyBase.
DR GO; GO:0006585; P:dopamine biosynthetic process from tyrosine; IBA:GO_Central.
DR GO; GO:0042417; P:dopamine metabolic process; IMP:FlyBase.
DR GO; GO:0008049; P:male courtship behavior; IMP:FlyBase.
DR GO; GO:0042136; P:neurotransmitter biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0048082; P:regulation of adult chitin-containing cuticle pigmentation; IMP:FlyBase.
DR GO; GO:2000274; P:regulation of epithelial cell migration, open tracheal system; IMP:FlyBase.
DR GO; GO:0042542; P:response to hydrogen peroxide; IDA:FlyBase.
DR GO; GO:0009611; P:response to wounding; IEP:FlyBase.
DR GO; GO:0040040; P:thermosensory behavior; IMP:FlyBase.
DR GO; GO:0043052; P:thermotaxis; IMP:FlyBase.
DR GO; GO:0035220; P:wing disc development; IMP:FlyBase.
DR CDD; cd03345; eu_TyrOH; 1.
DR Gene3D; 1.10.800.10; -; 1.
DR InterPro; IPR045865; ACT-like_dom_sf.
DR InterPro; IPR001273; ArAA_hydroxylase.
DR InterPro; IPR018301; ArAA_hydroxylase_Fe/CU_BS.
DR InterPro; IPR036951; ArAA_hydroxylase_sf.
DR InterPro; IPR036329; Aro-AA_hydroxylase_C_sf.
DR InterPro; IPR019774; Aromatic-AA_hydroxylase_C.
DR InterPro; IPR041903; Eu_TyrOH_cat.
DR InterPro; IPR005962; Tyr_3_mOase.
DR InterPro; IPR019773; Tyrosine_3-monooxygenase-like.
DR PANTHER; PTHR11473; PTHR11473; 1.
DR Pfam; PF00351; Biopterin_H; 1.
DR PIRSF; PIRSF000336; TH; 1.
DR PRINTS; PR00372; FYWHYDRXLASE.
DR SUPFAM; SSF55021; SSF55021; 1.
DR SUPFAM; SSF56534; SSF56534; 1.
DR TIGRFAMs; TIGR01269; Tyr_3_monoox; 1.
DR PROSITE; PS00367; BH4_AAA_HYDROXYL_1; 1.
DR PROSITE; PS51410; BH4_AAA_HYDROXYL_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Catecholamine biosynthesis; Cell projection;
KW Cytoplasm; Iron; Metal-binding; Monooxygenase;
KW Neurotransmitter biosynthesis; Oxidoreductase; Reference proteome.
FT CHAIN 1..579
FT /note="Tyrosine 3-monooxygenase"
FT /id="PRO_0000205566"
FT REGION 105..132
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 112..132
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 409
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT BINDING 414
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT BINDING 454
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT VAR_SEQ 60..130
FT /note="Missing (in isoform Hypodermal)"
FT /evidence="ECO:0000303|PubMed:2483109"
FT /id="VSP_000545"
FT CONFLICT 264
FT /note="P -> L (in Ref. 4; AAL49320)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 579 AA; 65996 MW; 416CF26E04087E85 CRC64;
MMAVAAAQKN REMFAIKKSY SIENGYPSRR RSLVDDARFE TLVVKQTKQT VLEEARSKAN
DDSLEDCIVQ AQEHIPSEQD VELQDEHANL ENLPLEEYVP VEEDVEFESV EQEQSESQSQ
EPEGNQQPTK NDYGLTEDEI LLANAASESS DAEAAMQSAA LVVRLKEGIS SLGRILKAIE
TFHGTVQHVE SRQSRVEGVD HDVLIKLDMT RGNLLQLIRS LRQSGSFSSM NLMADNNLNV
KAPWFPKHAS ELDNCNHLMT KYEPDLDMNH PGFADKVYRQ RRKEIAEIAF AYKYGDPIPF
IDYSDVEVKT WRSVFKTVQD LAPKHACAEY RAAFQKLQDE QIFVETRLPQ LQEMSDFLRK
NTGFSLRPAA GLLTARDFLA SLAFRIFQST QYVRHVNSPY HTPEPDSIHE LLGHMPLLAD
PSFAQFSQEI GLASLGASDE EIEKLSTVYW FTVEFGLCKE HGQIKAYGAG LLSSYGELLH
AISDKCEHRA FEPASTAVQP YQDQEYQPIY YVAESFEDAK DKFRRWVSTM SRPFEVRFNP
HTERVEVLDS VDKLETLVHQ MNTEILHLTN AISKLRRPF
